TY - JOUR
T1 - Maps of protein structure space reveal a fundamental relationship between protein structure and function
JF - Proceedings of the National Academy of Sciences
JO - Proc Natl Acad Sci USA
SP - 12301
LP - 12306
DO - 10.1073/pnas.1102727108
VL - 108
IS - 30
AU - Osadchy, Margarita
AU - Kolodny, Rachel
Y1 - 2011/07/26
UR - http://www.pnas.org/content/108/30/12301.abstract
N2 - To study the protein structure–function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of &gt; 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two points approximates the structural distance between their corresponding domains. We use these maps to study the spatial distributions of properties of proteins, and in particular those of local vicinities in structure space such as structural density and functional diversity. These maps provide a unique broad view of protein space and thus reveal previously undescribed fundamental properties thereof. At the same time, the maps are consistent with previous knowledge (e.g., domains cluster by their SCOP class) and organize in a unified, coherent representation previous observation concerning specific protein folds. To investigate the function–structure relationship, we measure the functional diversity (using the Gene Ontology controlled vocabulary) in local structural vicinities. Our most striking finding is that functional diversity varies considerably across structure space: The space has a highly diverse region, and diversity abates when moving away from it. Interestingly, the domains in this region are mostly alpha/beta structures, which are known to be the most ancient proteins. We believe that our unique perspective of structure space will open previously undescribed ways of studying proteins, their evolution, and the relationship between their structure and function.
ER -